Induction of steroidogenic enzyme genes by insulin and IGF-I in cultured adult human adrenocortical cells

Steroids. 1997 Feb;62(2):258-65. doi: 10.1016/s0039-128x(96)00223-1.


Insulin and the insulin-like growth factors (IGFs) have multiple role in gene expression in steroidogenic cells. We investigated the regulation of steroidogenic enzyme gene expression by insulin and IGF-I in primary cultures of human adrenocortical cells from donors of ages 19-77 years. The effects of insulin and IGF-I observed here were independent of age and sex of the donor. After 5 days in serum-containing medium, cultures were exposed to insulin or IGF-I together with cyclic AMP analogs or ACTH in serum-free defined medium. Insulin and IGF-I at physiological concentrations increased mRNA levels for 17 alpha-hydroxylase and type II 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) in the absence of cyclic AMP or ACTH. They had lesser effects on 21-hydroxylase and cholesterol side-chain cleavage enzyme mRNA levels and were3 without effect on 11 beta-hydroxylase mRNA. All steroidogenic enzyme mRNAs were strongly increased by cyclic AMP or ACTH, and this increase was potentiated by insulin or IGF-I. These effects of insulin and IGF-I were accompanied by decreases in the ratio of dehydroepiandrosterone/cortisol synthesized from pregnenolone by the cultures. Induction of steroidogenic enzyme genes in adult human adrenocortical cells by insulin and IGF-I is unlikely to occur by means of a cyclic AMP-dependent mechanism. These data increase the evidence for an important regulation of steroidogenesis by these hormones.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 17-Hydroxysteroid Dehydrogenases / genetics*
  • Adrenal Cortex / drug effects*
  • Adrenal Cortex / enzymology
  • Adrenal Cortex / metabolism
  • Adult
  • Cells, Cultured
  • Culture Media, Serum-Free
  • Cyclic AMP / metabolism
  • Dehydroepiandrosterone Sulfate / metabolism
  • Gene Expression Regulation, Enzymologic / drug effects*
  • Humans
  • Insulin / pharmacology*
  • Insulin-Like Growth Factor I / pharmacology*
  • Steroid 17-alpha-Hydroxylase / genetics*


  • Culture Media, Serum-Free
  • Insulin
  • Dehydroepiandrosterone Sulfate
  • Insulin-Like Growth Factor I
  • Cyclic AMP
  • 17-Hydroxysteroid Dehydrogenases
  • 3 (or 17)-beta-hydroxysteroid dehydrogenase
  • Steroid 17-alpha-Hydroxylase